A major effort of this project is directed toward the design and synthesis of highly specific and efficient immunomodulators. The current design principle is based on the signal amplification produced by polyvalent presentation of effector molecules and is closely allied with the immunon construct of Dintzis et al. Effector molecules (e.g., monoclonal antibodies directed against specific cell surface proteins) are multiply and covalent linked to soluble polymer carriers of very high molecular weight using heterobifunctional reagents. Various structural parameters are being varied in order to optimize the performance of these immunomodulators, and collaborative studies are in progress to explore their properties. So far these studies have dealt mainly with mitogenic stimulation of B cells by soluble conjugates of anti-IgD and anti IgM. Conjugates of class I MHC antigens with high polymers have been employed in studies of T-cell receptor-MHC interactions. New methods are being explored for linking antibodies through their polysaccharide chains to high molecular weight carriers. Another important aim of this project is to explore the property of general multispecificity of antibodies and other kinds of receptors. Studies are in progress to compare the frequency distribution of binding constants of monoclonal antibodies for large numbers of diversely structured substances. Additional studies will be directed at showing to what extent binding events from the above trials are representations of alternative modes of complementation in the binding site region of a given receptor. These findings will be related to specificity and other important functions of receptor-effector interactions and networks in the immune system.